Research

Viruses to study intrinsic innate immune response signal trasnduction.

cropped-5280407684_201625598f_o.jpgViruses express immune evasion molecules to inhibit the immune response.   These proteins are also virulence factors. As such, viral immune evasion molecules bridge the fields of immunology and virology.   Our lab is interested in studying immune evasion molecules expressed by poxviruses, including vaccinia virus (VACV), molluscum contagiosum virus (MCV) and monkeypox virus (MPX). These viruses are important for human health; VACV is the smallpox vaccine and is a vaccine vector. MCV causes a common skin infection in children, sexually active adults and immunocompromised patients. MPX causes a zoonotic disease (monkeypox) that is endemic to Africa.

We are particularly interested in identifying poxvirus proteins that inhibit a triad of intrinsic innate immune (IIR) responses: apoptosis, NF-kB activation and IRF3 activation. We have identified several of these proteins and we are now interested in asking how these proteins inhibit IIRs on a molecular level.

Our approach is to study these viral proteins in several different settings, including expression of proteins independent of infection, during infection in cultured cells and during infection of laboratory animals. This is a worthwhile area of investigation because it can identify novel mechanisms to control the signal transduction pathways involved in IIRs. This gives us the ability to design new approaches to control IIRs to our advantage, down-regulating IIRs in autoimmune disease or up-regulating IIRs to successfully cure infections or cancer.

 

Disinfecting viruses in drinking water to improve global health.

IMG_1041The World Health Organization (WHO) estimated in 2014 that 748 million people lack access to improved Drinking water sources globally, and that 1.8 billion people utilize a drinking water source that is fecally contaminated. These contaminated drinking water sources have a significant impact on public health due to the spread of waterborne pathogens. Diarrhea is the second leading cause of death for children under five globally, and the WHO estimates that 90% of these cases can be attributed to unsafe water, inadequate sanitation, and poor hygiene. Waterborne viruses are particularly concerning because of their ability to cause high levels of morbidity and mortality. Viruses are challenging to remove through common drinking water filtration methods, and different types of viruses are resistant to different disinfectants.

Adenovirus is a human pathogen found globally in water sources and is known for its high stability and long-term viability in the environment. There are over 60 known human serotypes that cause a variety of health effects including gastroenteritis, conjunctivitis, and respiratory disease. Adenovirus is second only to rotavirus as the leading cause of acute gastroenteritis in children worldwide. It is particularly challenging to remove from drinking water treatment because although it is rapidly inactivated by free chlorine, it is the most resistant virus known to monochloramine disinfection and low-pressure ultraviolet light inactivation, the disinfectants of choice for water treatment plants in the US. The reason why the virus is so resistant to these disinfectants, but so susceptible to free chlorine inactivation remains unknown.

The goal of this project is to use molecular biology and virology to identify the portion of the virus life cycle that is inhibited by free chlorine vs. monochloramine vs. low pressure ultraviolet light. We use this strategy as a means to identify how each disinfectant is functioning to inactivate adenovirus on a molecular level. This knowledge will provide us with a basis for developing new water treatment technologies to be used worldwide to inactivate adenoviruses, as well as other viruses, in drinking water supplies.

This work is in collaboration with Drs. Benito Marinas, Yi Lu, and Madhu Viniswanthi (UIUC) and is supported by a grant from the iSSE at UIUC.

New approaches to rapidly detect infectious viruses.

adenovirus-300x282Viruses are one of the most abundant microorganisms on the planet, infecting every form of life from humans to bacteria. Viruses are relatively stable in the environment, and circulate via air, water, soil, biological vectors, and fomites. Mammalian viruses, many zoonotic (i.e., transmitted to humans from other animals), are directly responsible for some of the worst diseases known to man (e.g., Ebola, HIV), and for common causes of morbidity and mortality around the world (e.g., Norovirus, Influenza). Detecting and controlling viruses continue to be grand challenges in science because so little is known about the fundamental properties of viruses and their interactions with the environment, and because they vary greatly with respect to their genomes and replication cycles.

Currently, the non-cellular molecular nature of viruses forces current molecular detection systems to rely on using antibodies to detect viral proteins, or quantifying viral genomic targets. However, none of these techniques address whether the virus is infectious or not, and thus cumbersome cell culture techniques, available for just a few viruses, remain the only current approach to test infectivity.

We are developing an innovative sensor that detects infective viruses, using aptamer-based technology. We are using aptamers to detect infections adenovirus particles, using colorimetric changes and dipstick technology as a rapid detection method. Adenovirus is transmitted by the fecal-oral route to cause diarrhea and also causes upper respiratory tract infections. The ultimate goal is to use this technology to accurately detect infectious adenovirus particles in untreated or treated water. Our immediate goal is to use this technology to assess water quality in real time, in countries where without centralized water treatment systems. Our communites that we work with are in Uganda, Tanzania and Kenya. In addition, this will greatly aid federal and state governments in determining if water treatment methods are providing safe water for US citizens in real time. Additionally, this tool will be of great value for This same technology can be transferred to the clinical setting, to rapidly detect and follow adenovirus infections in humans. An ultimate goal is to develop aptamer technology for other viruses that are important to human health, including Ebola virus.

This work is in collaboration with Drs. Benito Marinas, Yi Lu, and Madhu Viniswanthi (UIUC) and is supported by a grant from the iSSE at UIUC.

The effects of climate change on water quality and water-borne diarrheal diseases.

Safe and abundant water is necessary for healthy humans both directly (safe drinking water) and indirectly (crop and livestock security). However, climate change-related extreme events result in a disruption of traditional water use practices. During events of droughts and floods, people are forced to use contaminated water. In both cases, drinking unsafe water results in human morbidity and mortality.

Surprisingly, there is little understanding of how changes in availability of safe water as a function of increased uncertainty in climatic events impact human behavior with respect of water collection and usages, and how changes in human behavior affect the quality of water.

We are examining the relationship between water scarcity and abundance due to enhanced climatic variability, subsequent human adaptive responses regarding water collection/treatment practices, and the result of these practices on water quality, specifically quantifying water-borne viruses and bacteria. We have selected study sites in Nepal and Uganda, two land-lock countries that both rely on subsistence agriculture and livestock farming as primary economic activities, but each experience distinct climates. This comparison will allow us to assess how different cultures and ecological impacts affects the resilience of both urban and rural communities during droughts and floods.